rs1023990

Positions:

• chr12-71988467-A-G
• chr12-71988467-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173353.4(TPH2):​c.942-5972A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,066 control chromosomes in the GnomAD database, including 5,085 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5085 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502

Genes affected

TPH2 (HGNC:20692): (tryptophan hydroxylase 2) This gene encodes a member of the pterin-dependent aromatic acid hydroxylase family. The encoded protein catalyzes the first and rate limiting step in the biosynthesis of serotonin, an important hormone and neurotransmitter. Mutations in this gene may be associated with psychiatric diseases such as bipolar affective disorder and major depression. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPH2	NM_173353.4	c.942-5972A>G		intron_variant		ENST00000333850.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPH2	ENST00000333850.4	c.942-5972A>G		intron_variant		1	NM_173353.4	P1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39061 AN: 151946 Hom.: 5077 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.247

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.257 AC: 39085 AN: 152066 Hom.: 5085 Cov.: 32 AF XY: 0.255 AC XY: 18986 AN XY: 74346

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.244

Alfa AF: 0.254 Hom.: 614

Bravo AF: 0.264

Asia WGS AF: 0.235 AC: 817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1023990; hg19: chr12-72382247;